Chemotherapy Effect, Osteosarcoma, Survival, Toxicity, Drug
Conditions
Keywords
osteosarcoma, doxirubicin, cisplatin, methotrexate, ifosfamide, apatinib, camrelizumab
Brief summary
Treatment strategies for high-grade osteosarcoma with multidrug chemotherapy and resection result in 3-year event-free survival of 60-70%. The most common factors predicting survival are presence of metastases, histological response to preoperative chemotherapy and complete surgical resection. Four of the active drugs in osteosarcoma include cisplatin, doxorubicin, high-dose methotrexate and ifosfamide and this combination (MAPI), given preoperatively and postoperatively, is widely used for the treatment of osteosarcoma in China. Apatinib also has activity in advanced setting and when incorporated into the treatment of patients with metastatic disease seemed to improve progression-free survival. Combination of apatinib and camrelizumab resulted in durable therapuetic effect in selected cases. Though EURAMOUS-1 suggested that changing chemotherapy postoperatively on the basis of histological response did not improve outcomes. The exploratory study with radomised design to compare combination of chemotherapy with target drug or combination of chemotherapy with anti-PD-1 antibody versus standard chemotherapy has not been tried yet. Thus we aim to investigate the efficacy and toxicity of these combiantions versus standard chemotherapy in this study.
Interventions
DRUGMAPI chemotherapy
AP = Doxorubicin (Adriamycin) 37.5 mg/m2/day \* 2day (total/cycle 75 mg/m²) \+ Cisplatin 120 mg/m2/course (total/cycle 120 mg/m²) ; M = Methotrexate 12000 mg/m2 (total/cycle 12000 mg/m²) with leucovorin rescue; I = Ifosfamide 2400 mg/m2/day \*5day (total/cycle 12000 mg/m²)
DRUGApatinib Mesylate
anti-angiogenesis tyrosine kinase inhibitors 500 mg orally daily
DRUGCamrelizumab
anti-PD-1 antibody 200mg ivgtt. Q2W
Sponsors
Chinese Sarcoma Study Group
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed high-grade osteosarcoma, including second malignancies * Tumor (primary, metastatic, or both) resectable OR is expected to become resectable after neoadjuvant induction chemotherapy * Suitable for neoadjuvant chemotherapy and adjuvant chemotherapy * Performance status - Lansky 50-100% (for patients under 16 years of age); Performance status - WHO or ECOG 0-2 with a life expectancy \>3 months * normal cardiac function (shortening fraction \>28%), normal hearing, normal bone marrow as shown by an absolute neutrophil count of at least 1·5 × 10⁹ cells per L (or a white blood cell count of at least 3 × 10⁹ cells per L if neutrophil count is not available), and a platelet count of at least 100 000 platelets per μL * Patients were also required to have a serum bilirubin concentration of at most less than 1·5 times the upper limit of normal and a normal creatinine concentration for their age as per protocol * Women of child-bearing potential had to take adequate contraceptive measures and have a negative pregnancy test within 7 days of study entry.
Exclusion criteria
* patients who have recieved anti-angiogenic TKIs or anti-PD-1/PD-L1 antibodies * allergy to chemotherapy or apatinib or camrelizumab * other severe illness (eg, psychosis or previous history of cardiovascular disease) * symptomatic or known CNS metastases * previous or concurrent second primary malignant tumours * had uncontrolled complications such as diabetes mellitus, coagulation disorders, urine protein ≥ ++, and so on * had other infections or wounds * pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| event-free survival rate | 2 years | from initial treatment after definitive surgery to progression/death/ last follow up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| overall survival rate | 5 years | from initial treatment after definitive surgery to death/ last follow up |
Countries
China
Contacts
Primary ContactLu Xie, M.D.
Backup ContactXin Sun, M.D.
Outcome results
None listed